Sandra Witelson had studied scores of brains looking for gender differences. Then she found one that made a difference: Einstein's.

"Once you find this one difference," she remembered thinking, "it implies that there will be a cascade of differences."

As she systematically analyzed the brains in her refrigerator, she discovered that other neural structures seemed larger or smaller among men, depending on whether the man had been right-handed or left-handed.

They were relatively the same size in women. "The relationships that we were finding were always — and I do mean always — different for men and women," she said.

She narrowed her study to right-handed men and women, still looking for differences in microscopic anatomy between the left side of the brain and the right side. She meticulously counted the neurons in sets of tissue in which each sample measured 280 microns wide — about twice the thickness of a human hair — and 3 millimeters deep.

Staring through the microscope, she was baffled.

"I had the first two patients, and they were so very different," Witelson said. "I kept looking and looking at them, trying to see what the difference could be."

Then she consulted the donor documentation for each tissue sample. "Finally, I saw that one was a man, and one was a woman."

Among women, the neurons in the cortex were closer together. There were as many as 12% more neurons in the female brain.

That might explain how women could demonstrate the same levels of intelligence as men despite the difference in brain size.

"So among female brains, the cortex is constructed differently, with neurons packed more closely together," she said.

Witelson probed deeper. She knew that the human cortex was a sandwich of six layers, each packed with neurons.

She peeled away the sheets of the temporal lobe — a region associated with perception and memory — in several of her brain specimens. She discovered that the increased neural density occurred only on layers 2 and 4, which form the hard wiring for signals coming into the brain.

Then she analyzed the microscopic structure of the prefrontal cortex. There the crowding of neurons was evident only in layers 3, 5 and 6, which carry the wiring for outbound signals.

Just to be sure, she checked left-handed brains as well as right-handed brains. She found the same sex differences when she surveyed her left-handed brains.

Perhaps, she speculated, these neuron-rich layers in an area associated with perception and speech were the reason women scored more highly than men on tasks involving language and communication.

Slowly, she formed a theory: The brains of men and women are indeed different from birth. Yet the differences are subtle. They might be found only among the synapses in brain structures responsible for specific cognitive abilities.

For so long, scientists had championed the idea of larger brains as an indicator of intellect. Witelson, however, gradually became convinced that overall brain size didn't matter.

"One of the things that firmed it up for me," she recalled, "was the case of Einstein."

An Odd Pursuit

By taking Einstein's brain, Thomas Harvey had succumbed to an impulse older than medicine.